If you have ever heard, read or written the phrase “the patient is edematous but intravascular dry”, you have to check this review (doi.org/10.1186/s13054-023-0…) 👇 Fluid normally exchanges freely between the plasma and interstitial space and is returned to the “central circulation” primarily via the lymphatics. In disease states, such as sepsis, the return flow of fluid from the interstitial space to the plasma seems to be very slow, which promotes the well-known triad of "hypovolemia + hypoalbuminemia + peripheral edema" The authors discuss studies suggesting that there two key mechanisms contributing to this triad: (1) acute lowering of the interstitial pressure by inflammatory mediators such as TNFα, IL-1β, and IL-6 and, (2) nitric oxide-induced inhibition of the intrinsic lymphatic pumping As you know, fluid is filtered in the (pre-)capillary side and reabsorbed at the post-capillary end, right? Well, not really... According to the traditional model historically taught in introductory physiology and medical school (I still remember it...), in the precapillary (arteriolar) end, the high capillary hydrostatic pressure exceeds plasma oncotic pressure, causing net filtration of fluid out of the vessel into the interstitial space. In the post-capillary (venular) end, the hydrostatic pressure drops below plasma oncotic pressure, creating a net pressure gradient that causes reabsorption of ~90% of the filtered fluid back into the vessels. The remaining ~10% was thought to be drained by the lymphatic system According to the modern model (established via the discovery of the endothelial glycocalyx), in most tissues under normal, steady-state conditions, there is no sustained venular reabsorption. The endothelial glycocalyx layer acts as the primary semi-permeable filter. The effective oncotic gradient exists between the plasma and the subglycocalyx space, rather than the main interstitial fluid Under normal blood pressure, capillary hydrostatic pressure exceeds the effective opposing oncotic pressure across the entire length of continuous capillaries and post-capillary venules. Consequently, virtually all fluid filtered at the capillary level is picked up by the lymphatics, which then route the fluid through lymph nodes and return it to the venous system via the lymphatic ducts. Some exceptions exist in specialized vascular beds designed for continuous fluid absorption, such as the intestinal mucosa and renal peritubular capillaries. Also direct vascular reabsorption may occur temporarily during acute, severe drops in capillary hydrostatic pressure (e.g., severe hypovolemic shock or hemorrhage) to preserve plasma volume #foamed #foamcc #physiology